P828: NORMALIZATION OF HEMATOLOGIC AND HEALTH-RELATED QUALITY OF LIFE MARKERS IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA TREATED WITH PEGCETACOPLAN AND BASELINE HEMOGLOBIN AT OR ABOVE 10 G/DL
Authors: J. Panse, N. Daguindau, S. Okuyama, R. Peffault de Latour, P. Schafhausen, N. Straetmans, M. Al-Adhami, T. Ajayi, E. Persson, M. Yeh, R. Wong
Journal: HemaSphere (2022)

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare life-threatening disease characterized by chronic complement-mediated hemolysis and thrombosis. Patients living with PNH can experience anemia with associated fatigue, dyspnea, and require blood cell transfusions which can negatively impact quality of life (QoL). Pegcetacoplan (PEG), is a C3 complement-inhibitor approved by the FDA/EMA for adults with PNH. Aims: This post hoc analysis evaluated hemoglobin (Hb), lactate dehydrogenase (LDH), absolute reticulocyte count (ARC), and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue normalization rates and safety after PEG treatment in a subgroup of patients with PNH and baseline Hb levels ≥10.0g/dL from the PADDOCK (NCT02588833), PEGASUS (NCT03500549), and PRINCE (NCT04085601) studies. Methods: PADDOCK evaluated PEG treatment (270-360mg/day subcutaneously [sc]) in complement-inhibitor naïve patients. PEGASUS enrolled patients with Hb levels <10.5g/dL at screening despite stable eculizumab (ECU) treatment (≥3 months). PEGASUS patients were randomized 1:1 to ECU or PEG (1080mg sc 2x weekly) during the randomized controlled period (RCP) through Week 16. Patients who received PEG during the RCP continued with PEG monotherapy (PEG-to-PEG) and ECU patients switched to PEG monotherapy (ECU-to-PEG) during the open-label period (OLP) through Week 48. PRINCE compared PEG treatment (1080mg sc 2x weekly) in complement-inhibitor naïve patients with PNH and Hb levels below the lower limits of normal (males: ≤13.6g/dL; females: ≤12.0g/dL) to control treatment (CTRL; excluding complement-inhibitors i.e., ECU/ravulizumab). The post hoc analysis included adult patients with PNH with baseline Hb levels ≥10.0g/dL and no transfusions within 14 days of the baseline measurement. Hb, LDH, and ARC normalization, as well as FACIT-Fatigue normalization (defined as increase to population norm) was evaluated after 16 weeks of PEG monotherapy for all three studies. Patients who withdrew or were lost to follow-up without providing efficacy data at the specified timepoints were classified as non-responders. Safety endpoints included incidences of adverse events (AEs). Results: Overall, 22 patients were included in the post hoc analysis: 5 PADDOCK, 9 PEGASUS, and 8 PRINCE patients. After 16 weeks of pegcetacoplan treatment, patients in all three studies showed improvements in Hb normalization, LDH normalization, and ARC normalization (Table 1). Additionally, improvements in FACIT-Fatigue normalization were demonstrated in PADDOCK, PRINCE, and PEGASUS (PEG-to-PEG) patients (Table 1). No incidences of serious AEs were reported in PADDOCK and PRINCE subgroups. One PEGASUS patient had a serious AE of breakthrough hemolysis (severe, unrelated to PEG), following an upper respiratory infection which resolved and did not lead to study discontinuation. Incidences of injection site reactions and infections and infestations occurred at similar rates between subgroups in all three studies (Table 1). No thrombotic events occurred in this patient population. Image:Summary/Conclusion: While this patient population had near normal Hb at baseline (median: 10.4g/dL), they also had elevated ARC and LDH prior to PEG therapy, suggesting ongoing hemolysis which was normalized in most patients after PEG treatment initiation. Overall, these results suggest PEG can be efficacious long-term in patients with less severe anemia, regardless of prior complement-inhibitor treatment, resulting in further clinical improvements in markers of hemolysis and QoL. The safety profile of PEG was consistent with results from previous studies.